PROJECT SUMMARY The role of fat in breast cancer development and growth has been studied extensively using body mass index, a measure of whole body fatness, and dietary fat intake in a number of epidemiological studies. However, there is a paucity of studies, on an individual level, to assess the role of breast fat itself in breast cancer due to lack of a non-invasive and fast measurement method. Since breast fibroglandular cells are surrounded by breast fat cells, the characteristics of breast fat may have a stronger relationship with breast cancer development, as supported by recent studies showing that a majority of breast cancer develops at the interface between fibroglandular tissue and adipose tissue. However, it is not trivial to study the role of breast fat, mainly due to the lack of a non-invasive and fast measurement method sensitive enough to important features of breast fat, such as types of fat. Recently, we have developed a rapid MRI method, referred to as Gradient-echo Spectroscopic Imaging (GSI), to measure fatty acid composition during clinical breast MRI exams. GSI can provide map of saturated fat and unsaturated fats in the breast adipose tissue without performing tissue biopsy. Our pilot study found that the postmenopausal women with aggressive breast cancer, known as invasive ductal carcinoma, have a significantly higher percentage of saturated fat in their breast adipose tissue than the postmenopausal women with only benign lesions. The overarching goal of this study is to determine the role of saturated fatty acid in breast cancer development and growth. In this proposal, we plan to use GSI for non-invasive in vivo measurement of saturated fat in the breast adipose tissue of postmenopausal women who undergo diagnostic breast MRI exams (Aims 1 and 2) or MRI-guided biopsy scans (Aim 3). Our central hypotheses are that (i) the breast saturated fatty acid fraction measured by GSI is associated with the presence of malignant lesions in the breast and (ii) the breast saturated fatty acid fraction correlates positively with inflammation in the breast adipose tissue that may lead to increase in estrogen production in adipocytes. The proposed study will evaluate whether breast saturated fat is an independent risk factor for breast cancer, and whether it can provide additional diagnostic information to current clinical diagnostic exams. In addition, the proposed imaging measure of breast saturated fat can be used to assess the efficacy of any intervention to reduce cancer-related inflammation in the breast adipose tissue and to investigate the possible role of fatty acid composition in prevention and clinical management of breast cancer.